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Background: Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-age women. Excessive inflammation and elevated androgen production from ovarian theca cells are key features of PCOS. Human bone marrow mesenchymal stem cells (BM-hMSC) and their secreted factors (secretome) exhibit robust anti-inflammatory capabilities in various biological systems. We evaluated the therapeutic efficacy of BM-hMSC and its secretome in both in vitro and in vivo PCOS models., Methods: For in vitro experiment, we treated conditioned media from BM-hMSC to androgen-producing H293R cells and analyzed androgen-producing gene expression. For in vivo experiment, BM-hMSC were implanted into letrozole (LTZ)-induced PCOS mouse model. BM-hMSC effect in androgen-producing cells or PCOS model mice was assessed by monitoring cell proliferation (immunohistochemistry), steroidogenic gene expression (quantitative real-time polymerase chain reaction [qRT-PCR] and Western blot, animal tissue assay (H&E staining), and fertility by pup delivery., Results: BM-hMSC significantly downregulate steroidogenic gene expression, curb inflammation, and restore fertility in treated PCOS animals. The anti-inflammatory cytokine interleukin-10 (IL-10) played a key role in mediating the effects of BM-hMSC in our PCOS models. We demonstrated that BM-hMSC treatment was improved in metabolic and reproductive markers in our PCOS model and able to restore fertility., Conclusion: Our study demonstrates for the first time the efficacy of intra-ovarian injection of BM-hMSC or its secretome to treat PCOS-related phenotypes, including both metabolic and reproductive dysfunction. This approach may represent a novel therapeutic option for women with PCOS. Our results suggest that BM-hMSC can reverse PCOS-induced inflammation through IL-10 secretion. BM-hMSC might be a novel and robust therapeutic approach for PCOS treatment.

Primary ovarian insufficiency (POI), a condition in which there is a loss of ovarian function before the age of 40 years, leads to amenorrhea and infertility. In our previously published studies, we demonstrated recovery of POI, correction of serum sex hormone levels, increase in the granulosa cell population, and restoration of fertility in a chemotherapy-induced POI mouse model after intraovarian transplantation of human bone marrow-derived mesenchymal stem cells (hBM-MSCs). While hBM-MSC may be a promising cell source for treatment of POI, there are few reports on the safety of stem cell-based therapy for POI. For future clinical applications, the safety of allogenic hBM-MSCs for the treatment of POI through intraovarian engraftment needs to be addressed and verified in appropriate preclinical models. In this study, we induced POI in C57/BL6 mice using chemotherapy, then treated the mice with hBM-MSCs (500,000 cells/ovary) by intraovarian injection. After hBM-MSC treatment, we analyzed the migration of engrafted cells by genomic DNA polymerase chain reaction (PCR) using a human-specific ALU repeat and by whole-body sectioning on a cryo-imaging system. We examined the possibility of transfer of human DNA from the hBM-MSCs to the resulting offspring, and compared the growth rate of offspring to that of normal mice and hBM-MSC-treated mice. We found that engrafted hBM-MSCs were detected only in mouse ovaries and did not migrate into any other major organs including the heart, lungs, and liver. Further, we found that no human DNA was transferred into the fetus. Interestingly, the engrafted cells gradually decreased in number and had mostly disappeared after 4 weeks. Our study demonstrates that intraovarian transplantation of hBM-MSCs could be a safe stem cell-based therapy to restore fertility in POI patients.

Juvenile myelomonocytic leukemia (JMML), previously known as juvenile chronic myeloid leukemia (JCML), is a rare, myelodysplastic-myeloproliferative disease typically presenting in early childhood. This disorder is difficult to distinguish from other myeloproliferative syndromes such as chronic myeloid leukemia (CML) because of the similarities in their clinical and bone marrow findings. However, because of its unique biological characteristics such as absolute monocytosis with dysplasia, absence of Philadelphia chromosome or BCR-ABL fusion protein, hypergammaglobulinemia, and raised fetal hemoglobin level, this disorder does not satisfy the criteria for inclusion in the CML or chronic myelomonocytic leukemia (CMML) group, as seen in adult patients. We describe three cases of JMML, who had very similar clinical and laboratory findings., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

We report the case of a newborn presenting with hemolytic anemia, thrombocytopenia, hyperbilirubinemia, and renal failure in the first hours of life. An early plasmatherapy was undertaken, with good outcome. The specific von Willebrand factor-cleaving protease activity (ADAMTS 13 for a disintegrin and metalloprotease with thrombospondin type 1 repeats) was found to be low. This is the specific biologic diagnostic element of congenital thrombotic thrombocytopenic purpura (TTP). This disease of constitutional thrombotic microangiopathy is rare. The prognosis, usually life-threatening, was completely transformed given the better understanding of the pathogenesis of the disease and therapeutic progress., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objective: The purpose of this study was to compare clinical results of ICSI for different sperm morphology subgroups divided according to Kruger's classification system., Materials and Methods: This retrospectively study was conducted at Zeynep Kamil Training and Researching Hospital in Istanbul (Turkey). The study included 332 intracytoplasmic sperm injection (ICSI) cycles. The patients were under 37 years of age with primary infertility who were admitted to the Department of Reproductive Endocrinology and Infertility, from January 2005 to June 2009. The patients were divided in three groups based on Kruger's strict criteria. Normal sperm morphology was less than 4% in group 1, between 4-14% in group 2, and greater than 14% in group 3. All patients underwent ICSI and embryo transfer (ET) following controlled ovarian hyperstimulation (COH). The groups were compared to the rates of fertilization, implantation, clinical pregnancy, abortion, and live birth., Results: Pregnancy occurred in 132 (39.7%) of all ICSI cycles. There was no statistically significant difference between regarding groups regarding the rates of fertilization, implantation, clinical pregnancy, biochemical pregnancy, abortion, and live birth., Conclusion: The authors concluded that the normal sperm morphology defined by Kruger's strict criteria and sperm motility will not be able to predict prognosis of ICSI cycles.

In the last two decades, Klebsiella pneumoniae demonstrated some characteristics of acquisition of plasmids coding extended spectrum β-lactamases (ESBL). The review data showed an increase in worldwide prevalence of ESBL and a temporal shift in the prevalence of ESBL types in K. pneumoniae during this last decade. CTX-M-15 seems to be the predominant ESBL type in K. pneumoniae in some parts of the world. The dissemination of several nosocomial CTX-M-15-producing K. pneumoniae clones was reported unlike the worldwide dissemination of a single virulent ST131 CTX-M-15 producing Escherichia coli clone. The diversity of plasmids carrying the bla(CTX-M-15) gene in K. pneumoniae suggested the frequent transfer of this gene between different replicons. The acquisition of the bla(CTX-M-15) gene by K. pneumoniae was probably occurred via horizontal transfer from E. coli.

On a period of four years (january 1999-december 2002), 49 strains (non redundant) of extended spectrum beta-lactamase-producing Klebsiella pneumoniae from 43 hospitalised patients and three strains from the environment hospital were collected at Mongi Slim University Hospital Center. The objectives of our work were to investigate for clonality of strains, to clarify transmission fashions and reservoirs of the infection by reviewing clinical records and typing strains. Antibiotic susceptibility testing, plasmid analysis and Random Amplified Polymorphic DNA (RAPD) have been done. 84% of the patients were hospitalized in the intensive care and pediatric units. Urinary infections and septicaemias were the more frequent infections (74.2%). The 49 isolats have been classified in 13 antibiotypes. The plasmid analysis showed 16 patterns. The RAPD revealed 28 patterns and variation within patterns in five cases. Our results showed a diversity of the strains suggesting endemicity, possible transmission of plasmids and persistence of some clones which circulated between services. The used markers permitted the evaluation of a long-term strategy of prevention requiring a strict observance of hygiene rules and rational use of antibiotics.